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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purity, composition and in vitro fibrinolytic activity of four commercially available fibrinolytic agents, alteplase (recombinant tissue plasminogen activator, rt-PA, Actilyse; CAS 105857-23-6), streptokinase, urokinase and anistreplase (ansioyl-plasminogen-streptokinase activator-complex, APSAC), have been compared in this investigation. The fibrinolytic activity was measured in an in vitro thrombolytic assay. In this assay a human blood thrombus is dissolved in an environment of human plasma. This assay is representative for the in vivo situation, where plasminogen activation is also a limiting step in thrombolysis. In the in vitro thrombolytic assay alteplase is about 10 times more effective in clot lysis than either streptokinase or urokinase and more than 300 times more active than anistreplase. In addition, the ratio of active ingredient to total protein content in the preparations was analysed by RP-HPLC, SDS-PAGE, GPC-HPLC and amino acid analysis. The portion of active ingredient per total protein was 99.9% for alteplase, 55% for anistreplase, 20% for urokinase and 1% for streptokinase. This demonstrates that alteplase is the only fibrinolytic agent tested which is essentially free of protein additives of human origine and potential contaminants associated therewith. The superior purity of alteplase compared to the other fibrinolytics was confirmed by SDS-PAGE, RP-HPLC, and HPLC-GPC. Significant levels of aggregates were detected in streptokinase and urokinase preparations, whereas alteplase and anistreplase were essentially free of aggregates. These data demonstrate that there are significant differences in composition, purity and in vitro activity between different fibrinolytic agents.
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PMID:Quality aspects of fibrinolytic agents based on biochemical characterization. 181 Feb 68

A biodegradable and biocompatible polymeric system was developed for the controlled release of vancomycin for the treatment of brain abscesses. Poly(D,L-lactic acid) (PLA) and its copolymers poly(lactide-co-glycolide) PLGA 90:10 and PLGA 70:30, were prepared. Polymer disks containing vancomycin (VN) were prepared by solvent casting from methylene chloride solutions. Degradation of the polymer disk was studied by scanning electron microscopy, NMR and GPC. SEM revealed an increasing degree of degradation with time with both PLGAs, the effect being more distinct in the PLGA with the higher glycolide content (PLGA 70:30), which was confirmed with GPC, which showed both a decrease in the molecular weights of PLGA and a decrease in the heterogeneity index (chain length distribution) upon incubation in isotonic phosphate buffer at 37 degrees C for up to 5 weeks. NMR showed a decrease in the CH2 contents of the copolymers, implying that the glycolide component of the copolymers is being preferentially degraded. In situ, vancomycin release behaviour of the disks in pH 7.4 phosphate buffer saline (PBS) was followed for approximately 2 months in a static system. It was observed that release was according to Higuchi kinetics (Q vs. t(1/2)), and introduction of low molecular weight PLA or hydrophilic compounds like PEG increased the release rate.
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PMID:Vancomycin release from poly(D,L-lactide) and poly(lactide-co-glycolide) disks. 1181 62

Hexakis[p-(hydroxylmethyl)phenoxy]cyclotriphosphazene was synthesized by the reaction of hexachlorocyclotriphosphazene with the sodium salt of 4-hydroxybenzaldehyde and subsequent reduction of aldehyde groups to alcohol groups by using sodium borohydride. This compound was employed in initiating the ring-opening polymerization of epsilon-caprolactone and L-lactide to produce star-shaped poly(L-lactide) (PLA), poly(epsilon-caprolactone) (PCL), and their block copolymer with cyclophosphazene cores. 1H NMR and GPC analysis showed narrow-distributed star-shaped polyesters were successfully synthesized with high yields.
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PMID:Synthesis of the star-shaped copolymer of epsilon-caprolactone and L-lactide from a cyclotriphosphazene core. 1460 71

Temperature-sensitive diblock copolymers, poly(N-isopropylacrylamide)-b-poly(D,L-lactide) (PNIPAAm-b-PLA) with different PNIPAAm contents were synthesized and utilized to fabricate microspheres containing bovine serum albumin (BSA, as a model protein) by a water-in-oil-in-water double emulsion solvent evaporation process. XPS analysis showed that PNIPAAm was a dominant component of the microspheres surface. BSA was well entrapped within the microspheres, and more than 90% encapsulation efficiency was achieved. The in vitro degradation behavior of microspheres was investigated using SEM, NMR, FTIR, and GPC. It was found that the microspheres were erodible, and polymer degradation occurred in the PLA block. Degradation of PLA was completed after 5 months incubation in PBS (pH 7.4) at 37 degrees C. A PVA concentration of 0.2% (w/v) in the internal aqueous phase yielded the microspheres with an interconnected porous structure, resulting in fast matrix erosion and sustained BSA release. However, 0.05% PVA produced the microspheres with a multivesicular internal structure wrapped with a dense skin layer, resulting in lower erosion rate and a biphasic release pattern of BSA that was characterized with an initial burst followed by a nonrelease phase. The microspheres made from PNIPAAm-b-PLA with a higher portion of PNIPAAm provided faster BSA release. In addition, BSA release from the microspheres responded to the external temperature changes. BSA release was slower at 37 degrees C (above the LCST) than at a temperature below the LCST. The microspheres fabricated with PNIPAAm-b-PLA having a 1:5 molar ratio of PNIPAAm to PLA and 0.2% (w/v) PVA in the internal aqueous phase provided a sustained release of BSA over 3 weeks in PBS (pH 7.4) at 37 degrees C.
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PMID:Preparation and characterization of temperature-sensitive poly(N-isopropylacrylamide)-b-poly(D,L-lactide) microspheres for protein delivery. 1460 9

This paper focuses on the dependence of the rheological properties of PLA-PEG and PLGA dispersions and films on the polymer structural properties, in order to obtain useful information to predict and explain the performance of polyester films as drug-delivery systems. In this study, one PLA-PEG and three PLGA polymers of different molecular mass were synthesized and characterized by NMR, GPC, DSC and TGA-FT-IR. To characterize the viscoelastic behaviour of concentrated solutions in dichloromethane and of the films obtained by a solvent-casting technique, oscillatory shear rheometry was used. The polymer dispersions showed a characteristic Newtonian viscous behaviour, but with different consistency index depending on the nature of the polymer. Freshly prepared, PLGA and PLA-PEG films had elastic modulus (G') greater than viscous modulus (G"). The decrease in both moduli caused by an increase in temperature from 25 to 37 degrees C was especially marked for the polymers with T(g) below or around 25 degrees C (PLGA 27 kDa and PLA-PEG 27 kDa). After being immersed in pH 7.4 aqueous solution for one week, PLGA films showed a significant increase in both G' and G", due to the promotion of polymer-polymer interactions in a non-solvent medium. In contrast, the PLA-PEG film became softer and more hydrated, due to the amphiphilic character of the polymer. The water taken up by the film acted as a plasticizer and induced the softening of the system. These results suggest that the presence of PEG chains exerts a strong influence on the mechanical properties of polyesters films and, possibly, the performance as coating or matrices of drug-delivery systems.
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PMID:Structural properties of biodegradable polyesters and rheological behaviour of their dispersions and films. 1600 21

Paclitaxel is one of the best anticancer drugs, which has excellent therapeutic effects against a wide spectrum of cancers. The formulation of paclitaxel used in its currently clinical administration includes Cremophor EL, which has been found to cause serious side effects. Nanoparticle formulation of paclitaxel may provide an ideal solution for this problem and achieve a sustained chemotherapy. A novel copolymer, poly(lactide)-vitamin E TPGS (PLA-TPGS), was synthesized from lactide and d-alpha-tocopheryl polyethylene glycol 1000 succinate by bulk polymerization for nanoparticle formulation of anticancer drugs. 1H NMR, FTIR and GPC were used to detect molecular structure of the copolymer. Paclitaxel-loaded PLA-TPGS nanoparticles were fabricated by a modified solvent extraction/evaporation technique with or without emulsifier involved, which were characterized by laser light scattering for size and size distribution; field emission scanning electron microscopy for surface morphology; zeta potential for surface charge; X-ray photoelectron spectroscopy for surface chemistry. The drug encapsulation efficiency and the in vitro drug release kinetics were measured by high-performance liquid chromatography. Formulation optimization was pursued. The particles were found of around 300 nm in size and narrow size distribution. Of all, 89% drug encapsulation efficiency has been achieved for nanoparticles of 5% drug loading. The drug release from PLA-TPGS nanoparticles was found to be biphasic with an initial burst of 17% in the first day, followed by a sustained pattern with 51% release after 31 days.
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PMID:Nanoparticles of poly(lactide)/vitamin E TPGS copolymer for cancer chemotherapy: synthesis, formulation, characterization and in vitro drug release. 1602 75

Paclitaxel is one of the most effective antineoplastic drugs. Its current clinical administration is formulated in Cremophor EL, which causes serious side effects. Nanoparticle (NP) technology may provide a solution for such poisonous adjuvant problems and promote a sustained chemotherapy, in which biodegradable polymers play a key role. Our group has successfully synthesized novel poly(lactide)-tocopheryl polyethylene glycol succinate (TPGS) (PLA-TPGS) copolymers of desired hydrophobic-hydrophilic balance for NP formulation of anticancer drugs. The present work is focused on effects of the PLA:TPGS composition ratio on drug encapsulation efficiency, in vitro drug release, in vitro cellular uptake and viability of the PLA-TPGS NP formulation of paclitaxel. The PLA-TPGS copolymers of various PLA:TPGS ratios were synthesized by the ring-opening polymerization method and characterized by GPC and (1)H NMR for their molecular structure. Paclitaxel-loaded PLA-TPGS NPs were prepared by a modified solvent extraction/evaporation method and characterized by laser light scattering for size and size distribution, scanning electron microscopy for surface morphology and zeta potential for surface charge. High performance liquid chromatography was used to measure the drug encapsulation efficiency and in vitro drug release profile. Cancer cell lines HT-29 and Caco-2 were used to image and measure the cellular uptake of fluorescent PLA-TPGS NPs. Cancer cell viability of the drug-loaded PLA-TPGS was measured by MTT assay. It was found that the PLA:TPGS composition ratio has little effects on the particle size and size distribution. However, the PLA-TPGS NPs of 89:11 PLA:TPGS ratio achieved the best effects on the drug encapsulation efficiency, the cellular uptake and the cancer cell mortality of the drug-loaded PLA-TPGS NPs. This research was also carried out in close comparison with the drug-loaded PLGA NPs.
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PMID:The drug encapsulation efficiency, in vitro drug release, cellular uptake and cytotoxicity of paclitaxel-loaded poly(lactide)-tocopheryl polyethylene glycol succinate nanoparticles. 1656 85

Novel amphiphilic methoxy-poly(ethylene glycol)-poly(hexyl-substituted lactides) block copolymers were synthesized by ring-opening polymerization (ROP) of mono and dihexyl-substituted lactide (mHLA and diHLA) in bulk at 100 degrees C in the presence of tin(II) 2-ethylhexanoate (Sn(Oct)(2)) as catalyst and methoxy-poly(ethylene glycol) (MPEG) as initiator. MPEG-PmHLA and MPEG-PdiHLA copolymers of predictable molecular weights and narrow polydispersities were obtained, as shown by (1)H NMR and GPC. DSC experiments showed that the MPEG-PHLA block-copolymer presents a bulk microstructure containing MPEG domains segregated from the PHLA domains. Micelles were successfully prepared from these block copolymers, with sizes ranging from 30 to 80 nm. The critical micellar concentration (CMC) was found to decrease with the increasing number of hexyl groups on the polyester block (MPEG-PLA > MPEG-PmHLA > MPEG-PdiHLA) for copolymers of the same composition and molecular weight. The hydrophobicity of the micelle core in dependence of the number of hexyl groups along the PLA chain was evidenced by absorbance experiments with the incorporation of the dye Nile Red. These novel amphiphilic copolymers are interesting for micellar drug delivery and especially in regard to optimized hydrophobic drug loadings, as it was shown for griseofulvin as a model drug.
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PMID:Novel polymeric micelles for hydrophobic drug delivery based on biodegradable poly(hexyl-substituted lactides). 1671 91

Polylactic acid is a polymer of great technological interest, whose excellent mechanical properties, thermal plasticity, and bioresorbability render it potentially useful for environmental applications, as a biodegradable plastic and as a biocompatible material in biomedicine. This article discusses the synthesis and characterization of poly-L-lactic acid, obtained through two synthetic routes: direct polycondensation reactions without organic solvents, and in a supercritical medium. Tin complexes were used as catalysts in both polymerization reactions. The polymers were characterized by (1)HNMR, IR, GPC, DSC, and TGA techniques. In vitro biocompatibility tests were performed with human alveolar bone osteoblasts and there were assessed cell adhesion, proliferation and viability. The poly condensation reaction proved to be an excellent synthetic route to produce PLA polymers with different molar mass. The formation of polymers from lactic acid monomer was confirmed through techniques utilized. It was observed that cell adhesion and viability was not disturbed by the presence of the polymer, although the proliferation rate was decreased when compared to control.
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PMID:Chemical synthesis and in vitro biocompatibility tests of poly (L-lactic acid). 1743

To design novel bioinspired polymeric material, poly(D,L-lactic acid) (DL-PLA) was on the base and modified in the bulk. Firstly, maleic anhydride (MA) groups were introduced to the side chain of DL-PLA by the way of melting free radical copolymerization using benzoyl peroxide as an initiator. Then, to neutralize the acid generated during DL-PLA degradation, aliphatic diamine was immobilized by the N-acylation of anhydrides with butanediamine. As the following stage, adhesive peptides Arg-Gly-Asp-Ser (RGDS) were grafted into the backbone of DL-PLA by using carbodiimide as a coupling agent, in order to endow DL-PLA with bioactivity and biospecificity. The characterizations of the obtained polymers were by the means of GPC-MALLS, FTIR, (13)C NMR and XPS to explore the structures and rhodamine-carboxyl interaction method, ninhydrin reaction and amino acid analyzer to determine the content of MA, butanediamine, and RGDS, respectively, followed the test of pH changes during degradation in distilled water (pH = 6.45). Finally, the osteoblast behavior on different DL-PLA based films was investigated and the results indicated that the introduction of diamine could promote cell attachment and viability, and the incorporation of RGDS further improved its cytocompatibility. The synthetic DL-PLA based bioinspired material may have potentials for tissue engineering and other biomedical applications.
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PMID:Design of bioinspired polymeric materials based on poly(D,L-lactic acid) modifications towards improving its cytocompatibility. 1764 23


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